Synthesis and In Vitro Biological Evaluation of a Second-Generation Multimodal Water-Soluble Porphyrin-RAPTA Conjugate for the Dual-Therapy of Cancers.

ABSTRACT

In this study, we report the synthesis and biological evaluation of a novel cationic porphyrin-[Ru(η6-arene)(C2O4)PTA] (RAPTA) conjugate with potential as a multimodal dual-therapeutic agent. In the absence of high intensity light, relative to untreated cells our conjugate resulted in a 83% decrease in viable human adenocarcinoma cells at a concentration of 10 µM, which is significantly more active than the 57% decrease achieved with the same concentration of the unconjugated RAPTA complex alone. With a light dose of 20 J cm-2 (400-1200 nm) a reduction of 98% of viable cells was observed for the same concentration of conjugate. The conjugate is internalized by HT-29 cancer cells as proven by ICP-MS analysis and fluorescence microscopy; the latter result suggests that the conjugate has applications as a multimodal agent by acting as a fluorophore to obtain in vivo biodistribution data. Furthermore, the conjugate has an excellent relative singlet oxygen quantum yield, and the tetrapyrollic unit was found to be photostable under irradiation by either white light or red light.